Pancreatic transplantation reverses endothelial dysfunction in experimental diabetes mellitus.
BACKGROUND
There is insufficient evidence whether transplantation of the whole pancreas can reverse vascular complications associated with diabetes. In this study we investigated whether pancreatic transplantation in experimental diabetes reverses established defects in endothelium-dependent relaxation.


METHODS
Streptozotocin-induced diabetic rats underwent whole-pancreas transplantation after 12 weeks of disease. Endothelial function was evaluated 4 weeks after transplantation and compared with that of control- and age-matched diabetic animals. Blood was taken for analysis of glucose, insulin, total glycosylated hemoglobin, and plasma amino acid levels. Descending thoracic aortas were isolated, sectioned into rings, and mounted in isolated tissue baths. In precontracted rings, endothelium-dependent relaxation to acetylcholine was performed and compared with endothelium-independent relaxation to nitroglycerin as a control.


RESULTS
Pancreatic transplantation normalized the increases in glucose and total glycosylated hemoglobin levels and the decrease in serum insulin levels. Diabetes resulted in impaired relaxation to acetylcholine without altering relaxation to nitroglycerin. Pancreatic transplantation completely restored the defective relaxation to acetylcholine without altering the relaxation to nitroglycerin.


CONCLUSIONS
These results suggest that pancreatic transplantation selectively improved endothelium-dependent relaxation as opposed to a generalized improvement in vascular smooth muscle reactivity. Furthermore, these studies suggest for the first time that one aspect of vascular complications (i.e., endothelial dysfunction) is amenable to this surgical intervention.
Pieper
G M
GM
Department of Transplant Surgery, Medical College of Wisconsin, Milwaukee 53226, USA.
Adams
M B
MB
Roza
A M
AM
D000109:Acetylcholine / Q000494:pharmacology; D000596:Amino Acids / Q000097:blood; D000818:Animals; D001012:Aorta, Abdominal / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology*; D001786:Blood Glucose / Q000032:analysis; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000503:physiopathology* / Q000601:surgery*; D003925:Diabetic Angiopathies / Q000517:prevention & control; D004730:Endothelium, Vascular / Q000502:physiology / Q000503:physiopathology*; D006442:Glycated Hemoglobin / Q000032:analysis; D066298:In Vitro Techniques; D007328:Insulin / Q000097:blood; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology*; D005996:Nitroglycerin / Q000494:pharmacology; D016035:Pancreas Transplantation / Q000502:physiology*; D051381:Rats; D011917:Rats, Inbred Lew; D012016:Reference Values
D000109:Acetylcholine; D000596:Amino Acids; D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007328:Insulin; D005996:Nitroglycerin